ABSTRACT
Kras mutations are associated with pancreatic ductal adenocarcinoma (PDAC). Although tobacco smoking, pancreatitis, and obesity are known environmental risk factors for PDAC, the contribution of moderate alcohol intake to PDAC remains elusive. In the present study, we tested whether a combination of risk factors or moderate alcohol intake induces PDAC development in mice. Control Pdx1Cre and Pdx1Cre;LSL-KrasG12D mutant mice were fed a Western alcohol diet containing high levels of cholesterol and saturated fat, 3.5% alcohol, and lipopolysaccharide for 5 mo. In addition, mice were treated with cerulein, for induction of pancreatitis, and nicotine every month. Treatment with all of these risk factors promoted development of advanced pancreatic neoplasia and PDAC in the Pdx1Cre;LSL-KrasG12D mice but not in the control Pdx1Cre mice. Moderate alcohol intake or Western diet feeding also significantly promoted advanced neoplasia and PDAC development in Pdx1Cre;LSL-KrasG12D mice compared with mice fed a regular chow. Alcohol, but not Western diet, increased tumor development in the liver in the Pdx1Cre;LSL-KrasG12D mice, but its origin remained elusive due to leakiness of Pdx1Cre in hepatocytes. RNA-seq analysis revealed that alcohol feeding increases expression of markers for tumors (Epcam, Krt19, Prom1, Wt1, and Wwtr1), stroma (Dcn, Fn1, and Tnc), and cytokines (Tgfb1 and Tnf) and decreases expression of Fgf21 and Il6 in the pancreatic tumor tissues. Immunostaining showed heterogeneous expression of nephronectin, S100 calcium-binding protein A6, and vascular cell adhesion molecule 1 in pancreatic tumors surrounded by podoplanin-positive stromal cells. Our data indicate that moderate alcohol drinking is a risk factor for development of PDAC.NEW & NOTEWORTHY Heavy alcohol intake has been suspected to be a risk factor of pancreatic ductal adenocarcinoma (PDAC) in humans. However, the contribution of moderate alcohol intake to PDAC development remains elusive. In the present study, we experimentally show that moderate alcohol feeding significantly induces advanced stages of pancreatic intraepithelial neoplasia development and invasive PDAC in Pdx1Cre;LSL-KrasG12D mutant mice. Our data indicate that moderate alcohol drinking is a risk factor for PDAC.
Subject(s)
Alcohol Drinking/adverse effects , Carcinogens/toxicity , Carcinoma, Pancreatic Ductal/chemically induced , Central Nervous System Depressants/toxicity , Ethanol/toxicity , Pancreatic Neoplasms/chemically induced , Proto-Oncogene Proteins p21(ras)/biosynthesis , Proto-Oncogene Proteins p21(ras)/genetics , Animals , Carcinoma, Pancreatic Ductal/pathology , Ceruletide/pharmacology , Cytokines/metabolism , Diet, Western , Hepatocytes/metabolism , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/genetics , Liver Neoplasms/chemically induced , Mice , Mutation , Nicotine/pharmacology , Pancreatic Neoplasms/pathology , Trans-Activators/biosynthesis , Trans-Activators/geneticsABSTRACT
En el presente trabajo de investigación tiene su origen en los sucesos actuales de nuestro país, donde se va incrementando el interés del Profesional de Enfermería en realizar estudios de investigación. Uno de los enfoques que cuenta es la llamada investigación metodológica que la orienta a elaborar y demostrar la validez de instrumentos que garantice la recolección de datos confiables, precisos, objetivos y útiles para planificar, ejecutar y evaluar los cuidados de enfermería. En nuestro medio, específicamente en el área de la geriatría que maneja el servicio de Prestaciones de Atención Domiciliaria (PADOMI), donde constituye la atención preferencial que brinda ESSALUD en el domicilio a los pacientes con incapacidad para desplazarse a los Centros Asistenciales, con el objetivo de mejorar su calidad de vida y brindarles una atención digna. Surge de esta manera la necesidad de investigar sobre "Cual es la Validación de la Guía de Valoración para pacientes Adultos Mayores de Grado de Dependencia III durante la Visita Domiciliaria de Urgencias del Programa de Atención Domiciliaria - ESSALUD, 2009". Determinar la Validez de la guía de valoración para pacientes adultos mayores de Grado de Dependencia III durante la Visita Domiciliaria de Urgencias del Programa de Atención domiciliaria - ESSALUD, 2009. El presente estudio es de nivel aplicativo, tipo cuantitativo, método cuasi experimental transversal ya que permitirá obtener la Validez de la Guía de Valoración para Pacientes Adultos Mayores de Grado de Dependencia III durante la Visita Domiciliaria de Urgencias del Programa de Atención Domiciliaria-EsSalud. El área en que se realizara el estudio es en Urgencias-PADOMI el cual pertenece a EsSalud, ubicado entre Arenales y Domingo Cueto del Distrito de Lima Cercado. Dicha institución ofrece los servicios de atención de salud a pacientes geriátricos con enfermedades crónica. Para el desarrollo de los servicios mencionados, se cumple un horario de dos turnos que son guardia de día y guardia de noche. La población estará constituida por todas las enfermeras del área de Urgencias-PADOMI, son 35 enfermeras(os) por lo cual se tomara a todas y no se realiza muestra.
In the present research is rooted in current events in our country, which is also growing interest of Professional Nursing in research studies. One approach to consider is the so-called methodological research that aims to develop and demonstrate the validity of instruments to ensure the collection of reliable, accurate, objective and useful for planning, implementing and evaluating nursing care. In our area, specifically in the area of geriatrics who runs one of the Home Care Allowance (PADOMI), which is the preferential treatment provided at home ESSALUD the inability to move patients to the medical facilities with the objective to improve their quality of life and provide decent care. Thus arises the need for research on "What is the validation of the Patient Assessment Guide Grade Aging Unit III during the Emergency Home Visit Home Care Program - ESSALUD, 2009". Determine the validity of the assessment guide for elderly patients Grade III Unit at the Emergency Home Visit Home Care Program - ESSALUD 2009. The study is an application level, quantitative, quasi-experimental method which will produce transverse Validity Assessment Guide for Older Patients Unit Grade III for the Emergency Home Visit Home Care Program-ESSALUD. The area in which they conduct the study is in the ER, which belongs to PADOMI ESSALUD, located between Arenales and Domingo Cueto District of Lima Cercado. This institution offers health care services to elderly patients with chronic diseases. For the development of the services mentioned, it plays a schedule of two shifts that are guard day and night guard. The population is made up of all emergency nurses-PADOMI area, there are 35 nurses and hence will be taken to all and not done shows.